High-order brain interactions in ketamine during rest and task: a double-blinded cross-over design using portable EEG on male participants.

Ketamine is a dissociative anesthetic that induces a shift in global consciousness states and related brain dynamics. Portable low-density EEG systems could be used to monitor these effects. However, previous evidence is almost null and lacks adequate methods to address global dynamics with a small number of electrodes. This study delves into brain high-order interactions (HOI) to explore the effects of ketamine using portable EEG. In a double-blinded cross-over design, 30 male adults (mean age = 25.57, SD = 3.74) were administered racemic ketamine and compared against saline infusion as a control. Both task-driven (auditory oddball paradigm) and resting-state EEG were recorded. HOI were computed using advanced multivariate information theory tools, allowing us to quantify nonlinear statistical dependencies between all possible electrode combinations. Ketamine induced an increase in redundancy in brain dynamics (copies of the same information that can be retrieved from 3 or more electrodes), most significantly in the alpha frequency band. Redundancy was more evident during resting state, associated with a shift in conscious states towards more dissociative tendencies. Furthermore, in the task-driven context (auditory oddball), the impact of ketamine on redundancy was more significant for predictable (standard stimuli) compared to deviant ones. Finally, associations were observed between ketamine's HOI and experiences of derealization. Ketamine appears to increase redundancy and HOI across psychometric measures, suggesting these effects are correlated with alterations in consciousness towards dissociation. In comparisons with event-related potential (ERP) or standard functional connectivity metrics, HOI represent an innovative method to combine all signal spatial interactions obtained from low-density dry EEG in drug interventions, as it is the only approach that exploits all possible combinations between electrodes. This research emphasizes the potential of complexity measures coupled with portable EEG devices in monitoring shifts in consciousness, especially when paired with low-density configurations, paving the way for better understanding and monitoring of pharmacological-induced changes.

High-order brain interactions in ketamine during rest and task: A double-blinded cross-over design using portable EEG.

In a double-blinded cross-over design, 30 adults (mean age = 25.57, SD = 3.74; all male) were administered racemic ketamine and compared against saline infusion as a control. Both task-driven (auditory oddball paradigm) and resting-state EEG were recorded. HOI were computed using advanced multivariate information theory tools, allowing us to quantify nonlinear statistical dependencies between all possible electrode combinations. Results: Ketamine increased redundancy in brain dynamics, most significantly in the alpha frequency band. Redundancy was more evident during the resting state, associated with a shift in conscious states towards more dissociative tendencies. Furthermore, in the task-driven context (auditory oddball), the impact of ketamine on redundancy was more significant for predictable (standard stimuli) compared to deviant ones. Finally, associations were observed between ketamine's HOI and experiences of derealization. Conclusions: Ketamine appears to increase redundancy and genuine HOI across metrics, suggesting these effects correlate with consciousness alterations towards dissociation. HOI represents an innovative method to combine all signal spatial interactions obtained from low-density dry EEG in drug interventions, as it is the only approach that exploits all possible combinations from different electrodes. This research emphasizes the potential of complexity measures coupled with portable EEG devices in monitoring shifts in consciousness, especially when paired with low-density configurations, paving the way for better understanding and monitoring of pharmacological-induced changes.

Neuroscience from the comfort of your home: Repeated, self-administered wireless dry EEG measures brain function with high fidelity.

Recent advances have enabled the creation of wireless, "dry" electroencephalography (EEG) recording systems, and easy-to-use engaging tasks, that can be operated repeatedly by naïve users, unsupervised in the home. Here, we evaluated the validity of dry-EEG, cognitive task gamification, and unsupervised home-based recordings used in combination. Two separate cohorts of participants-older and younger adults-collected data at home over several weeks using a wireless dry EEG system interfaced with a tablet for task presentation. Older adults (n = 50; 25 females; mean age = 67.8 years) collected data over a 6-week period. Younger male adults (n = 30; mean age = 25.6 years) collected data over a 4-week period. All participants were asked to complete gamified versions of a visual Oddball task and Flanker task 5-7 days per week. Usability of the EEG system was evaluated via participant adherence, percentage of sessions successfully completed, and quantitative feedback using the System Usability Scale. In total, 1,449 EEG sessions from older adults (mean = 28.9; SD = 6.64) and 684 sessions from younger adults (mean = 22.87; SD = 1.92) were collected. Older adults successfully completed 93% of sessions requested and reported a mean usability score of 84.5. Younger adults successfully completed 96% of sessions and reported a mean usability score of 88.3. Characteristic event-related potential (ERP) components-the P300 and error-related negativity-were observed in the Oddball and Flanker tasks, respectively. Using a conservative threshold for inclusion of artifact-free data, 50% of trials were rejected per at-home session. Aggregation of ERPs across sessions (2-4, depending on task) resulted in grand average signal quality with similar Standard Measurement Error values to those of single-session wet EEG data collected by experts in a laboratory setting from a young adult sample. Our results indicate that easy-to-use task-driven EEG can enable large-scale investigations in cognitive neuroscience. In future, this approach may be useful in clinical applications such as screening and tracking of treatment response.

Age and sex related differences in orthostatic cerebral oxygenation: Findings from 2764 older adults in the Irish Longitudinal Study on Ageing (TILDA).

AIMS: Cerebral hypoperfusion is implicated in the pathogenesis of associations between orthostatic hypotension and adverse outcome such as falls, cognitive impairment, depression, and mortality. Although the blood pressure response to orthostasis has been well studied there is a lack of information on orthostatic cerebrovascular responses in older populations. METHODS AND RESULTS: We measured cerebral hemodynamics, utilizing near infrared spectroscopy, coupled with peripheral blood pressure during an active stand in a large population of well-phenotyped older adults (N = 2764). Multi-level mixed effect models were utilized to investigate associations with age and sex, as well as confounders including anti-hypertensive medications. Normative cerebral oxygenation responses were also modelled utilizing generalized additive models for location, scale, and shape (GAMLSS). Older age groups experienced larger initial drops in oxygenation and a slower recovery, and responses also differed by sex. The drop after standing ranged from -1.85 % (95 % confidence interval (CI): -2.02 to -1.68) in the males aged 54-59 years vs -1.15 % (95 % CI: -1.31 to -1.00) in females aged 54-59 years, to -2.67 % (95 % CI: -3.01 to -2.33) in males aged ≥ 80 years vs -1.97 % (95 % CI: -2.32 to -1.62) females aged ≥ 80 years. Reduced oxygenation levels were also evident in those taking anti-hypertensive medications. CONCLUSION: Cerebral autoregulation is impaired with age, particularly in older women and those taking anti-hypertensives. SBP during the stand explained some of the age gradient in the late recovery stage of the stand for the oldest age group. Reported orthostatic symptoms did not correlate with hypoperfusion. Therefore, measures of orthostatic cerebral flow should be assessed in addition to peripheral BP in older patients irrespective of symptoms. Further studies are required to investigate the relationship between NIRS measurements and clinical outcomes such as falls, cognitive impairment and depression.

Feasibility of Repeated Assessment of Cognitive Function in Older Adults Using a Wireless, Mobile, Dry-EEG Headset and Tablet-Based Games.

Access to affordable, objective and scalable biomarkers of brain function is needed to transform the healthcare burden of neuropsychiatric and neurodegenerative disease. Electroencephalography (EEG) recordings, both resting and in combination with targeted cognitive tasks, have demonstrated utility in tracking disease state and therapy response in a range of conditions from schizophrenia to Alzheimer's disease. But conventional methods of recording this data involve burdensome clinic visits, and behavioural tasks that are not effective in frequent repeated use. This paper aims to evaluate the technical and human-factors feasibility of gathering large-scale EEG using novel technology in the home environment with healthy adult users. In a large field study, 89 healthy adults aged 40-79 years volunteered to use the system at home for 12 weeks, 5 times/week, for 30 min/session. A 16-channel, dry-sensor, portable wireless headset recorded EEG while users played gamified cognitive and passive tasks through a tablet application, including tests of decision making, executive function and memory. Data was uploaded to cloud servers and remotely monitored via web-based dashboards. Seventy-eight participants completed the study, and high levels of adherence were maintained throughout across all age groups, with mean compliance over the 12-week period of 82% (4.1 sessions per week). Reported ease of use was also high with mean System Usability Scale scores of 78.7. Behavioural response measures (reaction time and accuracy) and EEG components elicited by gamified stimuli (P300, ERN, Pe and changes in power spectral density) were extracted from the data collected in home, across a wide range of ages, including older adult participants. Findings replicated well-known patterns of age-related change and demonstrated the feasibility of using low-burden, large-scale, longitudinal EEG measurement in community-based cohorts. This technology enables clinically relevant data to be recorded outside the lab/clinic, from which metrics underlying cognitive ageing could be extracted, opening the door to potential new ways of developing digital cognitive biomarkers for disorders affecting the brain.

Discrepancies in self-reported and actigraphy-based sleep duration are associated with self-reported insomnia symptoms in community-dwelling older adults.

OBJECTIVES: To establish agreement between self-reported and actigraphy-based total sleep time (TST). To determine the impact of self-reported sleep problems on these measurements. DESIGN: Cross-sectional study using data from Wave 3 of The Irish Longitudinal Study on Ageing (2014-2015). PARTICIPANTS: Community-dwelling older adults, aged ≥50 years, with self-reported sleep information and ≥4 days of actigraphy-based TST (n = 1520). MEASUREMENT: Self-reported total sleep time, daytime sleepiness, insomnia symptoms (trouble falling asleep, trouble waking too early) measured during a structured self-interview. Actigraphy-based total TST was collected using GENEactiv wrist-worn accelerometers. Demographic characteristics and health information were controlled for. Analyses included descriptive statistics, reliability and agreement analysis using paired t-tests, intra-class correlations and Bland-Altman analysis. Linear regression was used to model associations with measurement discrepancies. RESULTS: Participants reported that they slept 7.0 hours (SD: 1.4, Range: 2.0-13.0 hours) on average, compared to 7.7 hours (SD: 1.2 hours, Range: 3.0-13.0 hours) recorded by accelerometry. Trouble falling asleep or waking too early "most of the time" were associated with under-reporting of sleep by 2.3, and 2.2 hours respectively. Agreement between measurements had an intra-class correlation of 0.18 and wide 95% limits of agreement (-3.90 to 2.55 hours). Under-reporting of sleep was independently associated with insomnia symptoms. CONCLUSION: The agreement between self-reported and actigraphy-based TST in community dwelling older adults was low. Self-reported insomnia symptoms were independently associated with under-reporting of sleep. Studies seeking to measure sleep duration should consider inclusion of questions measuring experience of insomnia symptoms to account for potential influence on measurements.

Associations between cognitive function, actigraphy-based and self-reported sleep in older community-dwelling adults: Findings from the Irish Longitudinal Study on Ageing.

OBJECTIVE: Cognitive impairment is prevalent in older ages. Associations with sleep are well established; however, ambiguity remains in which sleep characteristics contribute to this impairment. We examined cross-sectional associations between both self-reported and actigraphy-based sleep and cognitive performance across a number of domains in community-dwelling older adults. METHODS: 1520 participants aged 50 and older with self-reported and actigraphy-based total sleep time (TST) (≤5, 6, 7-8, 9 and ≥10 h) and self-reported sleep problems were analysed. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), verbal fluency, immediate and delayed recall memory, colour trails tests, and choice reaction tests (CRT). Associations between sleep and cognition were modelled using linear and negative binomial regression. RESULTS: Negative associations were found between ≥10 h of self-reported TST and MoCA error rate (incidence rate ratio [IRR] = 1.42; 95% confidence interval [CI] = 1.18, 1.71; p < 0.001); verbal fluency (beta [B] = -2.32 words; 95% CI = -4.00, -0.65; p < 0.01); and delayed recall (B = -0.91 words; 95% CI = -1.58, -0.25; p < 0.05) compared to 7-8 h. Significant associations with actigraphy-based TST were limited to MoCA error rate in ≤5 h (IRR = 1.22; 95% CI = 1.02, 1.45; p < 0.05) compared to 7-8 h. Higher numbers of sleep problems were associated with slower performance in CRT cognitive response time (IRR = 1.02; 95% CI = 1.00, 104; p < 0.05) and total response time (IRR = 1.02; 95% CI = 1.00, 1.04; p < 0.05). CONCLUSIONS: Self-reported long sleep duration was consistently associated with worse cognitive performance across multiple domains. Marginal associations between cognition and both actigraphy-based sleep and self-reported sleep problems were also apparent. These results further affirm poor sleep as a risk factor for cognitive impairment.

Age and sex differences in frontal lobe cerebral oxygenation in older adults-Normative values using novel, scalable technology: Findings from the Irish Longitudinal Study on Ageing (TILDA).

AIMS: Near-infrared spectroscopy (NIRS) is a non-invasive, easy to apply, optical technology for measuring cerebral blood oxygenation, but there is lack of comprehensive population data to aid interpretation and clinical use. Given the importance of cerebral perfusion in the context of evolving guideline recommendations for more aggressive lowering of blood pressure (BP) in hypertension, even in the oldest old, understanding of normative NIRS values is timely. We estimated normative values of cerebral oxygenation measured by NIRS in a large community-dwelling population sample of adults aged > = 50 years (n = 3110). We hypothesized that measurements would be attenuated by cardiovascular risk factors. METHODS: Data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA) was utilized. Frontal lobe cerebral oxygenation was continuously measured via a Portalite, while participants rested in the supine position. Beat-to-beat BP was measured simultaneously. Normative data was modelled using generalized additive models for location, scale, and shape (GAMLSS). Multivariate linear regressions were used to examine associations with cardiovascular risk factors. RESULTS: All three measures of NIRS (TSI, O2Hb and HHb) declined with increasing age. O2Hb and HHb were significantly lower in males than females. Increased smoking, excess alcohol intake, a higher waist-hip ratio, diabetes, angina, congestive heart failure, transient ischemic attack and total cardiovascular disease burden were all associated with decreased cerebral oxygenation. CONCLUSION: We present for the first time, normative resting-state NIRS reference data from a large population, which contributes to clinical interpretation of NIRS and advances the use of NIRS as a standard clinical tool.

Impact of Standing Speed on the Peripheral and Central Hemodynamic Response to Orthostasis: Evidence From the Irish Longitudinal Study on Ageing.

Assessment of the cerebrovascular and cardiovascular response to standing has prognostic value for a range of outcomes in the older adult population. Studies generally attempt to control for standing speed differences by asking participants to stand in a specified time but little is known about the range of transition times observed. This study aimed to characterize how standing speed associates with cardiovascular and cerebrovascular measures following transition from supine to standing. Continuous cerebral oxygenation, heart rate, systolic and diastolic blood pressure were monitored for 3 minutes after transitioning from supine to standing. An algorithm was used to calculate the time taken to transition from existing Finometer data (from the height correction unit). Linear mixed-effects models were used to assess the influence of transition time on each of the signals while adjusting for covariates. Transition time ranged from 2 to 27 s with 17% of participants taking >10 s to stand. Faster transition was associated with a more extreme decrease 10 s after standing but improved recovery at 20 s for cerebral oxygenation and blood pressure. Standing faster was associated with an elevated heart rate on initiation of stand and a quicker recovery 10 to 20 s after standing. The speed of transitioning from supine to standing position is associated with cardiovascular and cerebrovascular response in the early period after standing (<40 s). Care should be taken in the interpretation of findings which may be confounded by standing speed and statistical adjustment for standing time should be applied where appropriate.

Objective Sleep Duration in Older Adults: Results From The Irish Longitudinal Study on Ageing.

OBJECTIVE: This study assessed the distribution and correlates of objective sleep duration in the older population in Ireland. DESIGN: Cross-sectional study using population-derived data from wave 3 of The Irish Longitudinal Study on Ageing. SETTING: Community-dwelling adults. PARTICIPANTS: Adults, aged 50 years and older, who wore an accelerometer for at least 4 days (N = 1533). MEASUREMENTS: Sleep was measured for at least 4 days in 1533 participants using a GENEActiv wrist-worn accelerometer device. Sleep parameters included total sleep time (TST) and self-reported sleep problems. TST was categorized as short and long sleep duration using US National Sleep Foundation guidelines. Linear and multinomial logistic regression models assessed sociodemographic, health, and behavioral correlates of sleep duration. RESULTS: Mean TST for the sample was 463 minutes (SD = 72.6 minutes). Of participants, 13.9% and 16.5% measured short and long sleep duration, respectively. TST decreased as sleep problems increased, as did durations recorded in summer compared to winter recordings. Advancing age was associated with longer sleep, as was antidepressant use. Retired/unemployed participants recorded longer TST and were more likely to record long sleep compared to employed participants. Fair/poor self-rated health and separated/divorced participants were more likely to record short sleep. Those reporting moderate or high physical activity were less likely to record short or long sleep, respectively, compared to those reporting low physical activity. Participants reporting a limiting disability were less likely to record long sleep. CONCLUSION: Average TST was within recommended guidelines; however, a significant subset of older adults recorded sleep duration outside of the guidelines. Independent demographic and health correlates of suboptimal sleep were identified, many of which are modifiable. Patients and clinicians should be aware of factors potentially influencing sleep patterns. Longitudinal analyses to confirm directionality of relationships with potential risk factors are warranted. J Am Geriatr Soc 68:120-128, 2019.